This invention relates to a process for detecting the presence of malignant and pre-malignant cells in humans which utilizes an antibody to oncofoetal deoxythymidine kinase (TK).
The expression of oncodevelopmental by transformed cells antigens is well-documented (Ibsen et al, Biochim. Biophys. Acta, 560, 243-280 (1979); Rees et al, Methods Can. Res., 18, 99-133 (1979) and may well be a characteristic feature of many malignancies. The pyrimidine nucleoside recycling enzyme closely associated with proliferation, TK, is particularly interesting in this regard since quantitative and/or qualitative changes in TK activity invariably accompany neoplastic transformation. Progressively increasing levels of TK activity and shifts toward enzyme variants with foetal-like characteristics were present in preneoplastic and neoplastic intestinal lesions induced in rats by 1,2-dimethylhydrazine (Salser et al, Cancer Res., 36, 3495-3498 (1976); Ball, et al, Cancer Res., 36, 2686-2689 (1976)). There were also increases in the levels of the more thermolabile foetal-like TK variant(s) in the surface and the crypt of the colonic mucosa from these animals, i.e., surface vs crypt=6:1, reminiscent of the expansion of the proliferative zone to the upper two-thirds of the colon seen in carcinogen-treated mice and in patients with predilection to or prior history of colon cancer (Maskens et al, J. Nat'l. Cancer Inst., 58, 1221-1224 (1977); Deschner, Z. Krebsforsch., 91, 205-216 (1978). These data suggest that during carcinogenesis TK variant(s), qualitatively distinguishable from normal TK, begin to appear in the premalignant intestines.
In man, oncofoetal TK's have been identified (a) in several different types of cancer on the basis of electrophoretic mobilities and various biochemical parameters similar to those of foetal liver enzyme (Taylor et al, J. Biol. Chem., 247, 1930-1935 (1972); Stafford et al, Biochim. Biophys. Acta, 277, 439-442 (1972)) and (b) in colonic flat mucosa (but not in colonic crypt), several colorectal tumors and a variety of other unrelated solid tumors by using antisera produced against 2100-fold purified colonic mucosal TK to demonstrate the antigenic cross-reactivities between term-placental TK and cytosolic TK's from the above mentioned tissues (Salser et al, Nature, 260, 261-263 (1976)).